Remimazolam Enables Faster Sedation Induction and Recovery Compared With Midazolam in Diagnostic Upper Gastrointestinal Endoscopy: A Multicenter Randomized Controlled Trial

Abstract

Background and Aims: Remimazolam, a new ultra-short-acting benzodiazepine, is a safe and effective option for procedural sedation. Nevertheless, to date, no study has directly compared remimazolam and midazolam in diagnostic upper gastrointestinal endoscopy. This study aimed to evaluate the efficacy and safety of remimazolam compared with those of midazolam in this setting. Methods: This multicenter, single-blind, randomized, positive-control, superiority, investigator-initiated phase III trial enrolled patients who were scheduled to undergo diagnostic upper gastrointestinal endoscopy at seven academic teaching hospitals from April 2023 to January 2024. Participants were randomly assigned to receive remimazolam or midazolam (1:1 ratio). The primary endpoint was total procedure time, defined as the duration from the first sedative administration to discharge. Results: Of 133 randomized patients, 132 (remimazolam group, n = 66; midazolam group, n = 66) underwent upper endoscopy with sedation. The total procedure time was significantly shorter in the remimazolam group (30.3 vs. 48.5 min, p < 0.001). Sedation-related times (i.e., induction, sedation, recovery, and discharge times) were also significantly shorter in the remimazolam group (all p < 0.001). The incidence of adverse events did not significantly differ between the groups; however, the incidence rates of hypotension, bradycardia, and paradoxical reactions were lower in the remimazolam group. When compared to previous sedation experiences, patient satisfaction was higher in the remimazolam group (p < 0.001). Conclusions: Compared with midazolam, the use of remimazolam in diagnostic upper gastrointestinal endoscopy allows for faster sedation induction and recovery, more rapid discharge, and higher patient satisfaction compared with previous sedation experiences, while maintaining a safety profile similar to that of midazolam. Trial registration: ClinicalTrials.gov (NCT05836545). © 2025 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.